Safety Study of Preimplantation Factor (PIF-1) to Treat Acute Steroid-Resistant Graft-Versus-Host Disease (GVHD) (PIF1GVHD)

Phase I Clinical Trial to Assess Safety of Synthetic Preimplantation Factor (PIF-1) in Patients With Steroid-Resistant Acute Graft-Versus-Host Disease (GVHD) After Allogeneic Hematopoietic Stem-Cell Transplantation

The primary goal of this study is to determine the safety and tolerability of a novel peptide - preimplantation factor (PIF-1) - in patients who develop acute steroid-resistant graft-versus-host disease (GVHD) after matched bone marrow transplant (BMT).

Following matched BMT, patients will be placed on standard GVHD preventive therapy (cyclosporine); those who do not respond to cyclosporine are placed on a high-dose steroid regimen for 3 days. Patients that do not respond to this standard treatment will be given PIF-1 subcutaneously for 14 days.

Clinical data and samples will be collected, during PIF-1 administration and for an additional three months thereafter, to examine the long-term effect of PIF-1 treatment on the patients' GVHD status.

Study Overview

• Status: Unknown
• Conditions: Graft Vs Host Disease
• Intervention / Treatment: Drug: Preimplantation factor (PIF-1)

Detailed Description

Allogeneic BMT is a well-established treatment modality for malignant and non-malignant hematological diseases. Mature donor T cells within the stem-cell graft are the main mediators of the beneficial immune effects, but they are also responsible for the induction of GVHD, which becomes the major cause of morbidity and mortality post-transplant. Acute GVHD occurs within a 100-day period post-transplant and generally is manifested by dermatitis, enteritis, and hepatitis. The treatment of GVHD continues to be a challenge. To eliminate undesirable host-derived hematopoietic elements before BMT, patients are traditionally treated with myeloablative conditioning regimens involving high-dose chemotherapy and total-body irradiation. Standard GVHD prophylaxis and therapy comprise drugs that cause generalized immune suppression and place patients in danger of opportunistic infections and tumor relapse. For acute GVHD prevention, cyclosporine is often used; however, it is frequently necessary to administer long-term high-dose steroids as well.

An acute GVHD patient's lack of response to steroids is associated with poor prognosis. The ideal prophylaxis treatment for BMT patients would be one that prevented the graft from attacking the host, and that modulated the host's immune response so that it would accept the transplant, while maintaining its ability to protect the body against opportunistic hostile agents.

Pregnancy is an immune paradox: it allows maternal (host) acceptance of a semi-allograft (embryo), while it does not cause graft-versus-host or host-versus-graft reactions against the host/mother, or immune suppression. Therefore, the pregnant immunological status is compatible with the desired immune profile in patients undergoing BMT. By replicating the immune profile present in pregnancy in BMT patients, we may be able to reduce the occurrence of GVHD-related morbidity and mortality rates.

Preimplantation factor (PIF-1) is a novel, embryo-secreted peptide whose synthetic version matches the native peptide's properties. PIF-1 appears to play an important role in mediating the maternal response to pregnancy in mammals. In preclinical studies, PIF-1 has been found to be effective in preclinical BMT-GVHD models, without apparent toxicity.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Hadassah Medical Organization

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 66 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute steroid-resistant GVHD post matched BMT

Exclusion Criteria:

• Morbidity unrelated to GVHD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; 6 steroid-resistant acute GVHD patients, post-matched BMT (serial)

Drug: Preimplantation factor (PIF-1); The study will include 6 patients and will last for at least six months. The first three patients will receive PIF-1 (0.5 mg/kg/day for 14 days) by subcutaneous injection. The dosage in the next three patients may be increased to 1 mg/kg/day for 14 days. Patients will be treated serially: each patient will be followed for 2 weeks after cessation of PIF-1 administration before the next patient begins PIF-1 administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of PIF-1 in steroid-resistant patients who develop acute GVHD, as evidenced by clinical and laboratory indices	within 90 days after first PIF-1 injection

Secondary Outcome Measures

Outcome Measure	Time Frame
Therapeutic effect of PIF-1 on participants' acute GVHD status, as determined by comparison with the clinical and laboratory indices before intervention	within 90 days after first PIF-1 injection

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Collaborators: BioIncept LLC
• Investigators: Principal Investigator: Reuven Or, MD, Bone Marrow Transplantation, Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, Ein Kerem, Jerusalem, Israel

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): January 1, 2018
• Study Completion (Anticipated): January 1, 2018

Study Registration Dates

• First Submitted: August 16, 2007
• First Submitted That Met QC Criteria: August 16, 2007
• First Posted (Estimate): August 17, 2007

Study Record Updates

• Last Update Posted (Estimate): June 11, 2015
• Last Update Submitted That Met QC Criteria: June 10, 2015
• Last Verified: August 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: PIF1BMT-HMO-CTIL